L-1-CBZ-PIPECOLINAMIDE synthesis

Yield:-

Reaction Conditions:

Stage #1:(S)-1-(carbobenzyloxy)-2-piperidinecarboxylic acid with O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate;N-ethyl-N,N-diisopropylamine in N,N-dimethyl-formamide at 20; for 0.5 h;
Stage #2: with ammonia in 1,4-dioxane;N,N-dimethyl-formamide for 2 h;

Steps:

89.1
Step 1: Benzyl (2S)-2-(aminocarbonyl)piperidine-l-carboxylate (WWl) A mixture of (2S)-l-[(benzyloxy)carbonyl]hexahydro-2-pyridinecarboxylic acid (1 eq), TBTU (1.3 eq), DIPEA (1.3 eq), in DMF (2 M) was stirred at R.T. for 30 min then ammonia in dioxane (4 M, 3 eq) was added and stirring was continued for 2h. The reaction mixture was diluted with EtOAc, washed sequentially with sat. aq. NaHCO₃ solution and brine. The solution was dried (Na₂SO₄), filtered and concentrated under reduced pressure. The crude was purified by crystallization from Et₂O giving a white solid. MS (ES) Ci₄HisN₂O₃ required: 262, found: 263 (M+H)⁺.

References:

ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A. WO2009/63244, 2009, A1 Location in patent:Page/Page column 112